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Selection of Drug-Resistant Variants in the Female Genital Tract of Human Immunodeficiency Virus Type-1-Infected Women Receiving Antiretroviral Therapy A. SI-MOHAMED1, M.-D. KAZATCHKINE1, I. HEARD1, C. GOUJON2, T. PRAZUCK3, G. AYMARD4, G. CESSOT5, Y.-H. KUO1‚6, M.-C. BERNARD1, B. DIQUET4, J.-E. MALKIN5, L. GUTMANN1, and L. BELEC*1. 1Hôpital Broussais, Paris, France; 2 Hôpital Rotschild, Paris, France; 3Hôpital de la Source, Orléans, France; 4Hôpital de la Pitié-Salpêtrière, Paris, France; 5Institut Alfred Fournier, Paris, France; and 6Columbia Univ. Coll. of Physicians and Surgeons, New York We investigated the presence of HIV-1 RNA, proviral DNA and antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1 infected women receiving antiretroviral therapy. The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the intensity of the antiretroviral regimen. However, proviral DNA was detected in approximately half of cervicovaginal lavages, independently of the presence of HIV-1 RNA and antiretroviral regimen. Theses findings suggest that the female genital tract is comprised of at least two cellular reservoirs of HIV-producing cells that respond differently to antiretroviral treatment. In cervicovaginal secretions of most women with persisting genital compartment viral replication, HIV variants exhibiting mutations associated with drug resistance against protease as well as RT pol genes were found. The resistant variants likely arose as a consequence of selective pressure by antiretroviral drugs that penetrate the female genital tract at suboptimal concentrations. In a few women, resistant variants originated from semen containing antiretroviral drug resistant variants deposited during intercourse with an infected sexual male partner, as indicated by positive Y chromosome PCR from cervicovaginal lavage. Our observations indicate that antiretroviral therapy is not effective in purging the female genital tract of cell-associated provirus and that antiretroviral drugs in the female genital tract exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists. The results provide a basis for bi-directionnal heterosexual transmission of drug resistant HIV-1 variants. Key Words: Drug-resistance, HIV-1, Vaginal secretions |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |